Prevention of ventilator associated pneumonia (VAP)

ABSTRACT

Ventilator associated pneumonia (VAP) may be prevented in a patient, or its occurrence reduced in a population of patients, by using an anti-VAP device or an anti-VAP material such as an anti-VAP mouthpiece that absorbs secretions. By reducing the problem of bacterial-containing secretions that otherwise build up in the airway of, and elsewhere in, the intubated patient, VAP can be prevented from occurring in intubated patients, such as patients intubated with an endotracheal tube (ETT) or a nasogastric tube. Anti-VAP mouthpieces also are useable in non-intubated patients to maintain oral hygiene.

RELATED APPLICATIONS

This is a continuation of U.S. application Ser. No. 13/181,843, filedJul. 13, 2011, entitled “Prevention of Ventilator Associated Pneumonia(VAP)”, which is a continuation-in-part of U.S. application Ser. No.11/217,667, filed Sep. 2, 2005, entitled “Prevention of VentilatorAssociated Pneumonia (VAP)”, which claims the benefit of U.S.Provisional Application No. 60/607,070, filed Sep. 3, 2004, entitled“Device and Methods to Prevent Ventilator Associated Pneumonia and toProvide Laryngeal Anesthesia During Mechanical Ventilation.”

FIELD OF THE INVENTION

This invention relates to treatment of patients who are intubated withan endotracheal tube (ETT), and especially to ventilator associatedpneumonia (VAP) undesirably associated with such intubation.

BACKGROUND OF THE INVENTION

Ventilator associated pneumonia (VAP) is a potentially preventable causeof pneumonia that occurs in patients who are endotracheally intubatedand mechanically ventilated for more than 48 hours. VAP may occur in upto 65% of patients in the intensive care unit (ICU) and is associatedwith an increase in morbidity and mortality. It is estimated that costof diagnosing and treating VAP exceeds 1.1 billion dollars annually.Young P J, Ridley S A, Ventilator-associated pneumonia, Diagnosis,pathogenesis and prevention, Anaesthesia 1999; 54(12):1183-97; MoreheadR S, Pinto S J, Ventilator-associated pneumonia, Arch Intern Med 2000;160(13):1926-36.

VAP is usually a bacterial nosocomial pneumonia, which was neitherpresent nor incubating at the time of endotracheal intubation. Causes ofVAP are multifactorial (FIG. 1). The diagnosis of VAP is difficult andexpensive. Controversy continues to exist in the methodology in making adefinitive diagnosis. Treatment is also controversial and the use ofempiric antibiotics is believed to have contributed to making theoverall treatment of true VAP more difficult. Patients developing VAPrequire additional testing to make the diagnosis and additionaltreatments. A major cost to the treatment is prolonging the timepatients require mechanical ventilation and thus care in the ICUsetting. This increased time of treatment in this setting is likely toactually increase the chances of additional complications includingdeveloping additional VAPs and antibiotic resistant organisms.

The microbiology of VAP consist of a combination of Gram positive, Gramnegative, and anaerobic organisms, most of which are ororpharyngeal orenteric in origin. As such a major mechanism believed to be responsiblefor the development of VAP is the microaspiration of pooledoropharyngeal secretions around the inflated cuff of an endotrachealtube (FIG. 2).

Despite the use of high volume low pressure (HVLP) endotracheal tubecuffs, there is clear evidence that small channels develop between theendotracheal tube cuff and the trachea, which allow passage ofsubglottic secretions into the lower respiratory tract. These channelsdevelop because small folds develop from incomplete expansion of theendotracheal tube cuff. Seegobin R D, van Hasselt G L, Aspiration beyondendotracheal cuffs, Can Anaesth Soc J 1986; 33(3 Pt 1):273-9. The numberof the folds or channels can be reduced if higher volumes are used toinflate the cuffs. However, higher volumes will result in higherpressures being created between the cuff and the tracheal mucosa thusplacing the tracheal mucosa at risk for necrosis.

One strategy to reduce VAP from pooled secretions has been to performcontinuous aspiration of subglottic secretions (CASS). A speciallydesigned endotracheal tube called the HI-LO® EVAC tube by Mallinckrodtallows for this. This endotracheal tube contains a separate dorsal lumenending in the subglottic space just above HVLP cuff. Fluid can bedrained along this channel with suction. When clinically studied, theincidence of VAP has been reduced from 29% to 13% with intermittentdrainage and 32% to 18% with continuous drainage. (Valles J, Artigas A,Rello J, Bonsoms N, Fontanals D, Blanch L, et al., Continuous aspirationof subglottic secretions in preventing ventilator-associated pneumonia,Ann Intern Med 1995; 122(3):179-86; Kollef M H, Skubas N J, Sundt T M, Arandomized clinical trial of continuous aspiration of subglotticsecretions in cardiac surgery patients, Chest 1999; 116(5):1339-46.) Themethod appears to result in major cost savings if its use were widespread. (Shorr A F, O'Malley P G, Continuous Subglottic Suctioning forthe Prevention of Ventilator-Associated Pneumonia: Potential EconomicImplications, Chest 2001; 119:228-35.) The disadvantage of this methodis that suction is required. Because endotracheal intubation occurs inmany non-ICU areas, suction is not readily available. Patients arelikely to be a most risk for aspiration from subglottic secretions veryearly after intubation especially when it is performed in less thanideal places such as on the wards, the emergency department, or in theprehospital setting. For example, over 55% of head-injured patientsrequiring intubation in the field or emergency department developmentpneumonia which might be from very early aspiration. (Livingston D H,Prevention of ventilator-associated pneumonia, Am J Surg 2000; 179(2ASuppl):12S-17S.) Furthermore, patients often require movement from theICU to other locations within the hospital in order to undergoadditional treatments or diagnostic studies. Continuous suction may notbe available during these times. In addition, maneuvers such as changingpatient position in a bed may serve to increase balloon channel size orrelationship between the HI-LO EVAC port and the pooled secretions thuscreating additional opportunity for aspiration.

A number of methods, which involve changes in cuff design, have reportedvarious degrees of success but none have undergone extensive clinicaltesting. One method has used a latex cuff, which appears to provide thesealing effectiveness of low volume high pressure cuffs without damageto the tracheal wall. (Young P J, Ridley S A, Downward G., Evaluation ofa new design of tracheal tube cuff to prevent leakage of fluid to thelungs, Br J Anaesth 1998; 80(6):796-9.) The addition of keeping the cuffat a constant pressure using a special inflation system adds to thedegree of protection. (Young P J, Basson C, Hamilton D, Ridley S A,Prevention of tracheal aspiration using the pressure-limited trachealtube cuff, Anaesthesia 1999; 54(6):559-63.) A modification of this cuffusing silicone has been studied in humans requiring tracheostomy andappears to decrease leakage of supraglottic fluid compared conventionalHVLP cuffs. (Young P J, Burchett K, Harvey I, Blunt M C, The preventionof pulmonary aspiration with control of tracheal wall pressure using asilicone cuff, Anaesth Intensive Care 2000; 28(6):660-5.) This tube andcuff are manufactured by Euromedical Industries and have been used aspart of the intubating laryngeal mask system.

Another cuff called the Portex Soft Seal HVLP cuff (Portex Ltd, HytheUK) has been tested against other HVLP cuffs in bench models and appearsto perform better in terms of reducing leakage around the cuff. (Young PJ, Blunt M C, Compliance characteristics of the Portex Soft Seal Cuffimproves seal against leakage of fluid in a pig trachea model, Crit Care(Lond) 1999; 3(5):123-26.)

Also a unique thin walled endotracheal tube has been designed in which atraditional air filled cuff is replaced by a series of circumferentialgills. During intubation, the tube is placed so that a number of thegills are above and below the vocal cords. This creates a seal forpositive pressure ventilation (up to 40 cm H2O of peak inspiratorypressure) as well as a barrier to supraglottic secretions.(Reali-Forster C, Kolobow T, Giacomini M, Hayashi T, Horiba K, Ferrans VJ, New ultrathin-walled endotracheal tube with a novel laryngeal sealdesign: Long-term evaluation in sheep, Anesthesiology 1996;84(1):162-72; discussion 27A.) Although tested in animals we are notaware of any clinical testing. It is unknown what type of reaction mightbe caused by the gills coming in contact with the vocal cords in termsof irritation.

Other device strategies to reduce or prevent VAP have been to embed theendotracheal tube with antimicrobials such as silver. This methodappears to reduce the bacterial load. (Hartmann M, Guttmann J, Muller B,Hallmann T, Geiger K, Reduction of the bacterial load by thesilver-coated endotracheal tube (SCET), a laboratory investigation,Technol Health Care 1999; 7(5):359-70) However, it is presumed that thesecretions must be in contact with the silver for sufficient periods oftime for its antimicrobial activity to be effective. In regards to this,intubation done in less than ideal circumstances where patients may beat greatest risk for microaspiration means that antibiotic embeddedsystems or tubes designed to prevent formation of biofilm might not beeffective in this time early time range.

Another major problem in the patient requiring endotracheal intubationand mechanical ventilation is the need for sedation due to the coughingreflexes induced by contact of the endotracheal tube and cuff withpoints of the supra and subglottic portions of the larynx. These pointsinclude the epiglottis, vocal cords, and tracheal mucosa. These reflexesare capable of producing such irritation and coughing as to requiresignificant systemic sedation. This degree of additional sedation canimpede physical and neurologic assessment of the patient and delayefforts for weaning of mechanical ventilation. This is of greatimportance because additional time spent utilizing mechanicalventilation will necessarily result in the incurrence of significantexpense and may potentially result in the development of VAP with all ofits complications and additional expense.

Methods/devices used to reduce the coughing reflex associated withendotracheal tubes include instilling local anesthetics through thelumen of the endotracheal tube. This method is believed to anesthetizeto carina of the tracheal-bronchial tree. One device was found on theinternet, which depicts a multilumen endotracheal tube allowing forinstillation of anesthetic agents such as lidocaine. These ports appearto end at various locations along the tracheal bronchial tree. It isassumed that intermittent administration and contact of anesthesia atthese points will provide sufficient anesthesia of the trachealbronchial tree in contact with the endotracheal tube as to significantlyblunt the coughing reflex.

Patent literature about prevention and/or reduction of ventilatorassociated pneumonia is as follows.

U.S. Patent Application No. 20030073625 was published Apr. 17, 2003, byRedman et al., for “Methods of preventing ventilator associatedpneumonia by oral administration of antimicrobial IB-367 peptides.”

U.S. Patent Application No. 20040079376 was published Apr. 29, 2004, byMelker, for “Endotracheal tube apparatus and method for using the sameto reduce the risk of infections.” A tube-in-tube endotracheal tubeapparatus is disclosed.

U.S. Patent Application No. 20050065141 was published Mar. 24, 2005, byOdlink et al., for “Carbapenems useful in treating and preventingpulmonary infections, pharmaceutical compositions thereof and modes ofadministration thereof.”

Conventional strategies to reduce VAP necessitate purchase of a separateendotracheal tube, which making implementation difficult especially ifVAP prevention strategies are to be performed in all settings at theearliest possible time. In addition, each conventional strategy isrelatively singular or limited in its ability to prevent VAP.

Also, in a well-known and practiced conventional approach for reducingVAP, nursing and support staff perform repetitive dental and oralhygiene on an intubated patient to attempt to address VAP-causingorganisms present in and on the patient's dentition including the gums(gingival) and nearby mucosa. However, this manual hygiene work onintubated patients is labor-intensive, and even so some of them stilldevelop VAP. Use of such techniques in the early stages of intubationsuch as in the pre-hospital and emergency department settings is notpractical. This is unfortunate because these are places where patientsare at major risks and where the normal microbial oral flora of thepatient rapidly changes to more virulent hospital-based pathogens.

SUMMARY OF THE INVENTION

The above problems and shortcomings have been addressed by the presentinvention. The present inventors have recognized that ventilatorassociated pneumonia (VAP) may be prevented in a patient (such as, e.g.,a human patient, a veterinary patient), or its occurrence reduced in apopulation of patients, by using a relatively-simple anti-VAP device oran anti-VAP material in a space that otherwise would be wherebacterial-containing secretions would form. By reducing the problem ofbacterial-containing secretions that otherwise build up in the airway ofthe intubated patient, VAP can be prevented from occurring in intubatedpatients.

In one preferred embodiment, the invention provides an anti-VAP system,comprising an anti-VAP device or an anti-VAP material, wherein thedevice or the material is sized and configured to be disposed in apatient airway which is intubated with an endotracheal tube (ETT), suchas, e.g., an anti-VAP system comprising a device attached or attachableto the ETT; an anti-VAP system wherein the device or the material istouching the ETT; an anti-VAP system wherein the device or the materialis in proximity to the ETT; an anti-VAP system wherein the device or thematerial is situated within a distance of 1 cm or closer to wheresecretions build up in the airway of the intubated patient; an anti-VAPsystem comprising an anti-VAP attachment mechanically attachable to, anddetachable from, the ETT; an anti-VAP system comprising a device that isa sponge or is spongy; an anti-VAP system comprising a foamablematerial; an anti-VAP system comprising a semisolid or a gel; ananti-VAP system wherein the device or the material remains in thepatient airway for at least an hour; an anti-VAP system wherein thedevice or the material comprises at least one selected from the groupconsisting of: an absorbing agent; an antibacterial agent; and ananesthetic agent; an anti-VAP system wherein the device or the materialis removable from the ETT separately without requiring removal of theETT; an anti-VAP system comprising an anti-VAP attachment configured toreceive an ETT through an elastic tubular member (such as, e.g., atubular member made of latex, silicone; a tubular member coated orembedded with one or more of bacteriocidal agents, bacteriostaticagents, anesthetics, absorbing agents, and compounds inhibiting biofilmformation; etc.) that covers a balloon of the ETT and/or covers someportion of ETT distal and/or proximal sections; an anti-VAP systemcomprising an anti-VAP attachment that includes at least one portthrough which may be delivered antibacterial and/or anesthetic agents,and/or absorbing agents to the intubated patient; an anti-VAP systemcomprising an anti-VAP attachment that comprises a sleeve into which anETT may be received, wherein a sleeved ETT fits through a patient'svocal cords and into the trachea and the sleeve spans the vocal cords;an anti-VAP system wherein an anti-VAP attachment is assembled onto anETT. In another preferred embodiment, the invention provides a device ormaterial that allows passage of a nasogastric tube (such as, e.g., adevice that covers the nasogastric tube; an anti-VAP system thatcomprises an anti-VAP device or material that partially recedes into theupper esophagus; an anti-VAP system that comprises a device that isplaceable as part of the nasogastric tube (such as, e.g., a device thatis placeable after placement of the nasogastric tube; etc.); etc.

In another preferred embodiment, the invention provides a method ofpreventing ventilator associated pneumonia (VAP) in a patient (such as,e.g., a human patient, a veterinary patient) needing endotracheallyintubation, comprising: disposing an anti-VAP device or an anti-VAPmaterial in a region where secretions otherwise build up in the airwayof the patient when intubated (such as, e.g., a disposing step thatcomprises attaching an anti-VAP attachment to an endotracheal tube; adisposing step that comprises placing an anti-VAP sponge or spongymaterial touching or near the ETT; a disposing step that comprisesfoaming an anti-VAP foamable material on or near the ETT; a disposingstep that comprises providing an anti-VAP material (such as a gel, apowder, a liquid, etc.) on or near the ETT; etc.), including, e.g.,methods wherein the disposing step is performed while the ETT is in theairway of the patient; methods wherein the disposing step is performedwith the ETT outside the airway of the patient; prevention methodswherein the patient does not develop bacterial nosocomial pneumonia;prevention methods wherein the patient does not develop Gram positive,Gram negative or anaerobic VAP organisms; methods further including astep of providing airway anesthesia; In another preferred embodiment,the invention provides a device or material that allows passage of anasogastric tube (such as, e.g., a device that covers the nasogastrictube; methods which use an anti-VAP device that allows passage of anasogastric tube (such as an anti-VAP device that is placeable as partof the nasogastric tube; a device that is placeable after placement ofthe nasogastric tube; etc.); etc.

The invention in another preferred embodiment provides a method ofreducing occurrence of ventilator associated pneumonia (VAP) in apopulation of patients endotracheally intubated, comprising: for eachpatient, disposing an anti-VAP device or an anti-VAP material in aregion where secretions otherwise build up in the airway of the patientwhen intubated (such as disposing performed before patient intubation;disposing performed after patient intubation; disposing performed amixture of before and after patient intubation), such as, e.g., methodscomprising attaching an anti-VAP attachment to an endotracheal tube;methods wherein microaspiration is reduced; methods whereinoropharyngeal bacterial load is reduced; etc.

Another preferred embodiment of the invention provides a method ofpreventing ventilator associated pneumonia (VAP) in a patient (such as,e.g., a human patient, a veterinary patient) needing endotracheallyintubation, comprising: disposing a space-occupying anti-VAP device or aspace-occupying anti-VAP material in a mouth and/or oropharynx of apatient when intubated, wherein the anti-VAP device or anti-VAP materialremains disposed therein during a period of intubation of the patient,and wherein the anti-VAP device or anti-VAP material is other than anendotracheal tube (ETT), such as methods in which silver embeddedmaterial (such as ribbons, pads, etc.) are disposed in an oropharynx ofan ETT-intubated patient.

A further preferred embodiment of the invention provides a method ofreducing or preventing colonization of the respiratory tract withgastrointestinal organisms, such as by, e.g., a device or material thatpartially recedes into the upper esophagus, whereby colonization of therespiratory tract with gastrointestinal organisms is reduced orprevented; etc.

In another preferred embodiment, the invention provides a method ofpreventing ventilator associated infection (such as, e.g., VAP) in apatient (such as, e.g., a human patient, a veterinary patient) needingintubation (such as, e.g., endotracheal intubation, nasogastricintubation), comprising: a) within an intubated patient, non-surgicallydisposing a controllably-removable space-occupying anti-infection deviceor a space-occupying anti-infection material in an open space whereotherwise infection-causing organisms would accumulate, and wherein theanti-infection device or anti-infection material is other than anendotracheal tube (ETT) or a nasogastric tube; b) removing theanti-infection device or anti-infection material from the intubatedpatient. In such methods there may be further provided a step c) ofsubsequently re-occupying the open space where otherwiseinfection-causing organisms would accumulate in the intubated patientwith an anti-infection device or anti-infection material.

The invention in a further preferred embodiment provides an anti-VAPsystem, comprising an anti-VAP device or an anti-VAP material, whereinthe device or the material is sized and configured to be disposed in apatient airway intubated with a nasogastric tube.

Another preferred embodiment of the invention provides a method ofreducing occurrence of ventilator associated pneumonia (VAP) in apatient whose esophagus is intubated with a nasogastric tube,comprising: disposing an anti-VAP device or an anti-VAP material in aregion where secretions otherwise build up in the airway of the patientwhen intubated with the nasogastric tube and where these secretions maycome from the esophagus.

The invention also provides in another preferred embodiment, a method ofpreventing VAP-causing oropharyngeal and tracheal secretions fromtraveling away from a first location in a patient to a second locationwhere said secretions can cause VAP, comprising: disposing a barrier(such as, e.g., a barrier that has an absorbing capacity of at least 1ml of secretions; a barrier that is a mouthpiece; etc.) in the patient,in a blocking position relative to the secretions in the first location,wherein the barrier is (1) an absorptive member and/or (2) a physicalbarrier; and physically blocking and/or absorbing the secretions frommoving towards the second location in the patient, wherein the blockingand/or absorbing step is performed by the barrier, such as, e.g.,inventive methods that include disposing a barrier that is a mouthpiecein a mouth of the patient and other inventive methods.

In another preferred embodiment, the invention provides a method ofpreventing VAP, comprising: disposing an absorptive mouthpiece in amouth of a patient intubated with an ETT or a nasogastric tube.

The invention in another preferred embodiment provides an anti-VAPdevice, comprising: a mouthpiece having a hole therein and shaped to bereceived into a mouth of a patient, wherein the patient may be intubatedwith an ETT or nasogastric tube; wherein the hole in the mouthpiece issized to accommodate an ETT or a nasogastric tube, such as, e.g.,inventive anti-VAP devices wherein the mouthpiece comprises an absorbentmaterial that absorbs VAP-causing secretions; and other inventiveanti-VAP devices.

The invention also provides, in another preferred embodiment, a methodof preventing VAP in a patient who is intubated with an ETT or anasogastric tube, comprising: in a vicinity of the tube, installing amechanical barrier to secretions, wherein the installed mechanicalbarrier has a secretions-accumulating capacity of at least 0.1 ml or 0.1gm of secretions, the method including steps performed by the installedmechanical barrier of: receiving secretions from the patient withoutdischarging any secretions back into the patient, and blockingsecretions so that no secretions pass the mechanical barrier, such as,e.g., inventive methods that comprise installing a mechanical barrierthat has a secretions-accumulating capacity of at least 1 ml or 1 gm ofsecretions; and other inventive methods.

The invention in another preferred embodiment provides an anti-VAPproduct for use in a patient who is intubated with an ETT or anasogastric tube, comprising: a solid member that has asecretions-accumulating capacity of at least 0.1 ml or 0.1 gm ofsecretions, and that when installed in the patient in a vicinity of thetube, is a mechanical barrier that entirely blocks passage ofsecretions, such as, e.g., inventive products in which the solid memberhas a secretions-accumulating capacity of at least 1 ml or 1 gm ofsecretions; inventive products which are presaturated and/or resaturatedwith chlorhexidine, hydrogen peroxide, or other microbials or othermedicinals for sustained contact and release to at least one dentitionor mucosal surface; inventive products wherein the solid member is aone-size-fits-all shape installable in adult patients irrespective oftracheal diameter; inventive products wherein the solid member is aone-size-fits-all shape installable in pediatric patients irrespectiveof tracheal diameter; inventive products wherein the solid member isformed of an absorbent material and of a thickness for completesecretions-retention when installed in the patient, and at least amajority of secretions that enter the solid member are retained by thesolid member while the solid member is installed in the patient;inventive products wherein the solid member retains all secretions thatenter therein; and other inventive products.

The invention in a further preferred embodiment provides an oral hygienemethod for a patient not intubated with an ETT or a nasogastric tube,comprising: disposing in the patient a mouthpiece device which isnon-surgically removable, wherein the device comprises a solid memberthat has a secretions-accumulating capacity of at least 0.1 ml or 0.1 gmof secretions, and maintaining oral hygiene and reducing anoropharyngeal bacterial burden that would be associated with aspirationpneumonia, performed by the disposed device, such as, e.g., inventivemethods wherein the mouthpiece device-disposing is an alternative totraditional oral hygiene including tooth brushing, flossing andantiseptic mouth rinses; inventive methods that include saturatingand/or resaturating the mouthpiece device with medicinals; and otherinventive methods.

In another preferred embodiment, the invention provides a method ofpreventing VAP in a patient intubated with an endotracheal tube or anasogastric tube, comprising: disposing in the patient a device that isnot the tube or any part of the tube, wherein the disposed device ismacroscopic-sized and participates in, and/or contributes to, preventingVAP, such as, e.g., prevention methods that include, after the disposeddevice has remained in the intubated patient for a period of time,non-surgically removing the disposed device from the patient.

BRIEF SUMMARY OF THE DRAWINGS

FIG. 1 is a chart showing a common pathway to development of VAP bothearly and late after intubation of a patient. The present invention isuseful in both situations to reduce VAP.

FIG. 2 is a cross-sectional view of pooled secretions in the subglotticspace 200 (i.e., the space between inflated endotracheal balloon andvocal cords VC), which represents the problem when the invention is notin use. FIG. 2 shows a traditional endotracheal tube ETT with a pilotballoon for cuff inflation. The tube ETT is shown in relation to thesupraglottic space 203, the distal trachea 205, and the subglottic space200.

FIGS. 3 and 4 are cross-sectional views of an inventive open-endedsleeve through which an ETT is placed.

FIG. 5 is a cross-sectional view of the sleeve of FIG. 3 modified toinclude ports for delivery of compounds such as antimicrobials andanesthetics.

FIG. 6 shows an inventive sleeve containing its own balloon andinflation mechanisms.

FIG. 7 shows an inventive sleeve in which conventional barrierstrategies such as gills additionally may be used.

FIGS. 8 and 9 are views of an inventive anti-VAP attachment that allowsfor suctioning of the subglottic space or delivery of hydrogels or othercompounds to the subglottic space to obliterate the space and act as anadditional barrier.

FIG. 10 shows an inventive sleeve ETT attachment that isolates thesupraglottic area preventing passage of secretions to the subglotticspace.

FIGS. 11-14 show inventive anti-VAP foam ETT attachments.

FIG. 15 shows an inventive anti-VAP system using a foam or sponge ball.

FIGS. 16 and 17 show respective top view 1700T and side view 1700S ofball 1700 of FIG. 15.

FIG. 18 shows a non-hydrated sample (left) 1800 next to a thinned sample(right) 1801.

FIG. 18A shows a thinned sample (left) 1801 next to a hydrated thinnedsample (right) 1802.

FIG. 18B shows a thinned product (left) 1801 with ends 1803, 1804 bentinto an inventive circular sleeve (right) 1805 with the ends 1803, 1804sutured together.

FIG. 18C shows a thinned sample (left) 1810 made into an inventivesleeve (middle) 1811, with the inventive sleeve 1811 placed over anendotracheal tube (right) 1899.

FIG. 19 is a side view of an inventive anti-VAP mouthpiece device 1900in an open position.

FIG. 19A is a top view of the inventive device 1900 of FIG. 19.

FIG. 19B is a front view of the inventive device 1900 of FIG. 19.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT OF THE INVENTION

The invention provides anti-VAP activity by controlling the space(namely, at and/or near (such as within about 1 cm of) the ETT of anintubated patient, such as space 208 in FIG. 2) where, if uncontrolled,VAP-causing agents otherwise accumulate and proceed to cause VAP. Theaccumulation of such secretions may be appreciated by referring to FIG.2, which depicts (when the invention is not in use) pooled secretions inthe subglottic space 200 (the space between the inflated endotrachealballoon and the vocal cords VC). This pooling results in microaspirationaround the inflated endotracheal tube cuff 204 through small channelscreated between the cuff 204 and tracheal mucosa. Leakage 208 occurs ofsubglottic secretions through channels created from incomplete ETTballoon inflation. Such leakage 208 leads to VAP, as the presentinventors have recognized.

In the invention, the space at and/or near the ETT (such as the space209 of accumulating subglottic secretions in FIG. 2) is subjected toaffirmative anti-VAP control, such as by occupying the space (such as byan anti-VAP device or an anti-VAP material (such as, e.g., a foam,liquid, gel, sponge, hydrogel, biomaterial, etc.)). For example, aspace-occupying anti-VAP material or anti-VAP device is caused to occupythe space at and/or near the ETT, and the space-occupying material ordevice after a time is further controlled (such as by removing such aspace-occupying anti-VAP material or anti-VAP device after a time).Subsequently, the space may be further controlled, such as by againcausing the space to be re-occupied with an anti-VAP space-occupyingmaterial or device (which is not required to be the same as the removedanti-VAP material or device).

An anti-VAP material or anti-VAP device is not necessarily required tobe treated or coated or to include an organism-killing agent. Ananti-VAP material or anti-VAP device may, for example, merely provide asite for VAP-causing organisms to accumulate, with the site beingremovable from the patient before the accumulated VAP-causing organismscan cause VAP.

Examples of anti-VAP devices that may be used in an anti-VAP systeminclude, e.g., attachments or adjuncts that can be added to anyendotracheal tube before and in some cases after intubation, such as ananti-VAP device that is a sleeve. An anti-VAP device that is anattachment to an ETT advantageously removes problems of switching to aspecific new endotracheal tube, and further increases the potential toreduce VAP by multiple and combined means, again without relying on thespecifics of the underlying endotracheal tube used. An anti-VAPattachment to an ETT also advantageously allows for more flexibility asnew materials and methods evolve in airway management including theprevention of VAP. An anti-VAP device may be disposable or may bereusable after treatment (such as sterilizing treatment).

An example of an anti-VAP device is a disposable sleeve. The disposablesleeve may be provided to surround the endotracheal tube balloon and/ormore proximal sections of the tube.

Another example of an anti-VAP device is an elastic tubular member. Whenusing the inventive elastic tubular member, there also may be practicedconventional strategies to reduce the potential for small longitudinalfolds to occur upon endotracheal tube cuff inflation, such as, e.g.,constructing the ETT balloon with other materials such as latex orsilicone to reduce the formation of these channels or by eliminating theballoon altogether and replacing it with “gills”. However,advantageously, the inventive elastic tubular member can be used withvarious endotracheal tubes and thereby the invention advantageouslyprovides practical flexibility. An ETT may be placed through aninventive elastic tubular member that covers the native balloon and someportion of the distal and proximal ETT. This inventive tubular membercould be made, e.g., of latex, silicone or other materials, which arecoated or embedded with sliver or other bacteriocidal/static agents aswell as anesthetics. These materials might be made in a manner orcontain compounds inhibiting the formation of biofilms. The materialsfrom which to form the inventive tubular members may be made to displayvarious innate or induced electrostatic charges, which have beendemonstrated to favorably affect inflammation and bacterial growth. Thematerials from which to form the inventive tubular members could allowfor exogenous delivery (through ports in the sleeve) of antibacterial oranesthetic agents.

Anti-VAP devices and anti-VAP materials are not necessarily exclusive ofeach other. For example, an anti-VAP material may be formed into or usedwith an anti-VAP device. Importantly, the present invention is notlimited to solids and non-solids may be used in practicing the inventivecontrol of space where VAP-causing organisms otherwise accumulate.“Material” broadly includes any form, such as solids, liquids, foams,hydrogels, semi-solids, etc.

According to the invention, preferably a physical barrier (mostpreferably, an absorbent physical barrier that absorbs the secretions)is established where secretions (such as VAP-causing secretions) willencounter the physical barrier and be prevented by the physical barrierfrom moving from one location (such as, e.g., in a subglottic space, inthe oropharynx, etc.) to another location elsewhere in the patient wheretheir presence is likely to be even more problematic. The inventionprovides, for example, capture of VAP-causing secretions within apatient where an absorbent material disposed within the patient capturesthe secretions, after which the absorbent material removed after havingspent time (such as a time on the order of about an hour, a time on theorder of about two hours, etc.) in the patient absorbing secretions. Forexample, an inventive mouthpiece comprising an absorbent material isinserted in a patient's mouth and left inserted for a time during whichthe mouthpiece acts as a physical barrier encountered by the secretionsand absorbs secretions (such as, e.g., at least 0.1 ml of secretions,preferably at least 1 ml of secretions), after which the usedmouthpiece, that contains the captured secretions, is removed by medicalpersonnel from the patient's mouth.

Example 1 (Leakage Experiment)

Experimentation regarding anti-VAP devices and/or anti-VAP materials wasperformed as follows.

7 mm ETT inflated in the barrel of 20 cc syringe, with dye leakingoccurring around the cuff through channels formed between the cuff andthe balloon: A photograph was taken that shows a screening methodologyreported in other studies that uses the barrel of a 20 cc syringe to actas the trachea. It is intubated with an endotracheal tube followed byinflation of the cuff and introduction of dye above the balloon. A 7 mmETT was used. Leakage of dye around the balloon can then be observedfor. Leakage of dye is seen when the balloon is filled with 10 cc air.

7 mm ETT with rubber latex cover around the balloon, according to anembodiment of the invention; native balloon inflated: In anotherphotograph, another 7 mm ETT is used but before insertion into the“trachea” it was placed through a simple piece of a latex rubber drain.Inflation of the native balloon followed by instillation of dye was thenperformed. There is no evidence of leakage, even with manipulation ofthe proximal ETT. Identical results have been found using the fingerportion of simple latex gloves. The tubular member may be constructed insuch a manner that it comes with its own inflation port. Sleeves may bemade with portions of the sleeve (which surround the ETT native balloon)expanding as the native balloon is inflated or these sleeves couldcontain their own balloon and inflation mechanisms. Inflation mechanismsmay include, e.g., filling the sleeve balloon with self-expanding foamsimilar to that of the Bivona foam cuff product line. Again the sleevesmay be coated with various materials or could have channels and portsallowing the delivery of various beneficial agents.

Example 2

FIG. 3 shows an inventive open ended sleeve 500 or condom to be placedover an ETT prior to intubation. A portion 501 of the sleeve 500 goesover the ETT balloon and expands as the balloon expands.

Modification of the end of the sleeve 500 allows for the native balloonto be covered with a material that would not lead to formation ofchannels between the ETT attachment and the tracheal mucosa when thenative balloon is inflated. The sleeve 500 may be embedded withantimicrobials/bacteriostatic agents and anaesthetics. Materials usedfor forming the sleeve 500 preferably are resistant to formation ofbiofilms.

FIG. 4 shows the inventive sleeve 500 extending from below the balloonto the proximal tube when the sleeve 500 is used with a traditionalendotracheal tube ETT with a pilot balloon for cuff inflation. Theendotracheal tube ETT, supraglottic space 203, vocal cords VC, andsubglottic space 200 in FIG. 4 are as in FIG. 2. The sleeve 500optionally may have a separate inflation port (not shown) for theballoon cover portion.

Example 2A

FIG. 5 is a modified version of the sleeve 500 of FIG. 3, modified toinclude ports 709 for delivery of compounds (such as antimicrobials,anesthetics, etc.) and port 708 for injection of compounds (such asanesthetics, antimicrobials, etc.).

Example 2B

The inventive sleeves may have a conventional barrier technology such as“gills” (e.g., Reali-Forster et al, supra) attached to them. Forexample, a sleeve 500 (of FIG. 3) may have gills 909 added as shown inFIG. 7, to increase the barrier function of the sleeve 500.

Example 3

Referring to FIG. 6, the inventive sleeve 800 (which may contain specialcompounds) contains its own balloon 801 (which may be made of, e.g.,silicone, latex, or other material resistant to the formation ofchannels) and inflation mechanisms. The open-ended sleeve 800 or condomis placed over the ETT prior to intubation. The sleeve 800 contains itsown balloon 801 expanded with air or containing foam which self-expands.Pilot balloon and stem 809 for inflation of the sleeve balloon are shownin FIG. 6. The sleeve balloon 801 also may contain foam sponge similarto Bivona strategy and foam sponge deflated by aspiration, and theninflated when exposed to atmospheric pressure. The stem 809 is thenattached in line to a ventilator circuit. That is, the ports of theballoons 801 are hooked in line with the ventilator circuit so thatadditional expansion takes place during mechanical ventilation. Theballoons 801 may be coated with antimicrobials and anesthetics.

Example 4

An anti-VAP attachments may include, e.g., a sleeve containing a suctionand/or delivery port so that subglottic secretions could be suctioned.Alternatively, the subglottic space could be obliterated by injectingvarious water-soluble hydrogels or foaming agents containingbacteriostatic and anesthetic properties to act as a barrier and tobathe the mucosa and vocal cords. This could be exchanged daily bysuctioning and then injecting new material. Agents conventionally usedfor wound care may be applied.

In FIG. 8, a suctioning ring attachment 1000 is shown, that may beplaced around an ETT either before or after patient intubation. Port1009 in FIG. 8 is a suctioning port or delivery port. The inventivesleeve in FIG. 8 includes a near circumferential opening 1008 of thering connecting to the port 1009 for suctioning or delivery of hydrogelbarrier or other materials.

Example 4A

FIG. 9 shows another inventive port-containing sleeve, shown afterintubation of the ETT. As in earlier figures, the following arecomparably numbered: the endotracheal tube ETT which may be atraditional endotracheal tube, the supraglottic space 203, the vocalcords VC, the subglottic space 200, the inflated endotracheal tube cuff204 and distal trachea 205.

In FIG. 9, sleeve port 1109 is for injection of additional hydrogel tofill both supraglottic and subglottic space. The port 1109 may alsocontain conductive materials to produce various charges around thesleeve.

The ETT sleeve has ports 1108 to allow for extrusion of hydrogel intothe supraglottic space 203 and subglottic space 200. Injected hydrogel(or other material) 1107 obliterates subglottic space 200 providing abarrier function and delivery of antimicrobial, anesthetic, and othercompounds.

Example 5

As seen with reference to FIG. 10, another example of an inventiveanti-VAP attachment to a tube ETT is a sleeve 1200 allowing isolation ofthe supraglottic area similar to that of the laryngeal mask airway. Thedevice of FIG. 10 includes a flexible covering 1206 allowing delivery ofaerosolized or other forms of anesthetics or antimicrobials to the supraand sublottic areas. Optionally, the device may be modified to allow forsuction and could be formed to fit over or surround the epiglottissimilar to a laryngeal mask airway.

Sleeve part 1208 is a covering that may fit over theepiglottis/supraglottic area similar to a laryngeal mask airway.Optionally an inflatable balloon may be used to make the seal around thesupraglottic area.

The sleeve 1200 may contain antimicrobials and anesthetics. Suctioningmay take place through this anti-VAP device. In addition, this anti-VAPdevice may allow for delivery of agents to the supra and immediatesubglottic area such as anesthetic or antibacterial aerosols. Port 1209is for introduction of compounds (such as aerosolized compounds,antimicrobials, anesethetics, etc.) to the supraglottic and subglotticspace, or suctioning.

Again, as mentioned for other anti-VAP sleeves, this anti-VAP sleeve maybe coated with or contain antimicrobials, bacteriocidal and anestheticagents, etc.

An example of a prototype that was made and photographed is a thinnedproduct bent into an inventive circular sleeve with the ends suturedtogether. Then the inventive sleeve was placed over an endotrachealtube.

Example 6

The invention also provides anti-VAP foam/sponge sleeves (such as woundfoams/sponges which contain dyes and other material which can bebacteriostatic) that may be attached and then activated causing them toswell to obliterate the subglottic space. The foam absorbs secretionsand increases contact time of bacteria with a bactericidal agent used inor with the foam. The foam may traverse the vocal cords.

Referring to FIGS. 11-14, ETT attachments (such as the foam/hydrogelsleeve 1300 in FIG. 11) which may be made of foam are shown. Foam ETTattachments expand when placed into contact with moisture. The foam maybe embedded with antimicrobials or anesthetics. The sleeves shown inFIGS. 11-14 show a strategy in which a barrier function and drugdelivery are provided.

In FIG. 11, an endotracheal tube ETT wearing a foam/hydrogel sleeve 1300is shown prior to intubation. Through a hydrogel sleeve port 1309, theremay be injected water, additional hydrogel, or other activating agents.FIG. 11 shows a non-hydrated status of the sleeve 1300.

In FIG. 12, a medical foam material sleeve 1400 assembled on an ETT isactivated to an expanded state below the trachea 14. A stem 1409 isprovided to the sleeve 1400 allowing hydration.

In FIG. 13, a sleeve 1500 (such as a sleeve comprising hydrogel,non-hydrated medical foam, or another material) is assembled on an ETT,in an unactivated state, and spanning the vocal cords VC. A stem 1509 tothe sleeve 1500 permits hydration.

In FIG. 14, an activated sleeve 1600 (such as a hydrogel sleeve) isshown spanning the vocal cords VC, and expanding to consume most of thesubglottic space forming an impenetrable barrier. A stem 1609 to thesleeve 1600 permits hydration. The hydrate foam or other material of thesleeve 1600 spans through the vocal cords VC essentially eliminating thesubglottic space.

Example 7

A foam/sponge ball or other shaped member (sleeve) with a hollow coremay be placed around the ETT. This ball or sponge sleeve may be gentlycompressed and slid far down into the supraglottic area of theoropharynx where it acts act as a super absorber of secretions. The foammay be embedded with antimicrobials of various sorts and optionally maycontain and anesthetic. It may be nonadherent and thus friendly to theepiglottis. The foam ball, sleeve, or ring may be replaced at regularintervals.

Referring to FIG. 15, a foam/sponge ball 1700 is shown, but alternatelya non-ball shape may be used, preferably a shape that conforms to theentire posterior pharynx. Ball 1700T is the top view and ball 1700S isthe side view of the oropharyngeal foam ball 1700. The ball 1700 acts asa secretion barrier and absorbs secretions. The ball 1700 may be loadedwith anesthetics and/or antimicrobials/bacteriostatic agents. The ball1700 is removable and replaceable.

Example 8

The invention may be applied to nasogastric tubes (esophageal andoropharyngeal portions), to reduce aerodigestive colonization to whichnasogastric tubes otherwise contribute. Anti-infection devices andanti-infection materials (such as, e.g., removable, disposableanti-infection devices and anti-infection materials) may be used tocontrol the space within a patient intubated with a nasogastric tube inthe space where otherwise infection-causing organisms would accumulate.

The inventive devices, materials, systems and methods discussed hereinwith references to the figures are especially preferred for use withhuman patients but also are useful in veterinary embodiments. In anexample of using the invention during intubation, by comparison to astandard endotracheal tube that passes through the vocal cords, aninventive non-hydrated sleeved endotracheal tube passes through thevocal cords and into the trachea, with the sleeve spanning the vocalcords. In another example of using the invention, an inventive hydratedsleeve is on an endotracheal tube, with the sleeve spanning the vocalcords.

In practicing the invention, one or more inventive anti-VAP device(s)may be used alone, or with one or more anti-VAP material(s). Theinventive anti-VAP methods, systems and devices may be used to reducemicroaspiration, reduce oropharyngeal bacterial load, and/or to provideairway anesthesia.

In the inventive methods and in using the inventive devices and systems,optionally suctioning may be performed. For example, an anti-VAP devicemay be used that allows suctioning from around close proximity of theETT (such as above the ETT balloon).

Example 9

Because a major source of VAP causing organisms can reside in and on thepatient's dentition including the gums (gingival) and nearby mucosa, inthis example, an inventive anti-VAP device (such as, e.g., an anti-VAPmouthpiece device 1900) is constructed for use in the oral cavity.Advantageously, use of an anti-VAP mouthpiece device in an intubatedpatient minimizes or avoids the need for the well-known and practicednursing maneuver, directed at reducing VAP, of performance of repetitivedental and oral hygiene on the patient which involve brushing thepatient's teeth and/or swabbing of the oral surfaces repetitively withantiseptic solutions such as chlorhexidine. The use of an anti-VAPmouthpiece device advantageously reduces this mentioned labor intensiveeffort while also providing more continuous antibacterial coverage oforal surfaces, which is a great benefit to the intubated patient as wellas to the nursing and support staff.

Examples of materials useable for this anti-VAP mouthpiece device are,e.g., sponge materials, hydrogel materials, other materials describedhereinabove for making an anti-VAP device, etc. Such materials mayabsorb oral secretions and provide antibacterial actions. They may alsobe presaturated and/or resaturated with antimicrobial agents such aschlorhexidine, hydrogen peroxide and other agents which can be releasedover time onto dental and mucosal surfaces.

In this example, the sponge or hydrogel material or other material formaking an anti-VAP device is formed into a form of a mouthpiece whichcovers dental and proximal mucosal surfaces of an intubated patient. Theanti-VAP mouthpiece device absorbs secretions, and preferably also killsbacteria and maintains oral and dental hygiene on a continuous basis.

The inventive anti-VAP mouthpiece device provided in this exampleconforms to the teeth and gingiva of the patient, along the lines of amouthpiece worn by a football player or snorer. Preferably themouthpiece covers most of the buccal, lip and sublingual/lingual mucosaof a patient as well as the hard and soft palate mucosa.

Optionally, portions of the mouthpiece may extend and come into contactwith the deeper posterior pharynx as well.

The mouthpiece addresses the organisms and secretions from the gums anddentition of patients which are a major source of organisms.

Use of a mouthpiece device according to this example would greatlyreduce the labor of carrying out oral hygiene in patients on amechanical ventilator.

A preferred use of inventive anti-VAP mouthpiece devices is in intubatedpatients. Another use of inventive anti-VAP mouthpiece devices is innon-intubated patients such as nursing home patients to preventaspiration pneumonia especially in patients whose oral hygiene is poor.This use may also enhance the overall oral hygiene of patients whocannot provide themselves, or be provided, routine oral hygiene. Use ofthe device may lead to improved oral and dental health.

Example 9A

In this example, inventive anti-VAP mouthpiece device 1900 (FIGS.19-19B) is provided comprising an upper plate 1901, center-hole 1902,lower plate 1903, upper segment 1911, lower segment 1913 and side wings1904. Preferably the upper plate 1901 covers the patient's hard/softpalate surface. The upper segment 1911 receives the patient's upperdentition and gingival. Through an open center-hole 1902, passage ispermitted of an endotracheal tube or nasogastric tube. Preferably thelower plate 1903 covers the patient's tongue surface. The lower segment1913 receives the patient's lower dentition and gingival. Side wings1904 cover buccal mucosa and preferably comprise an absorptive material.

Optionally, upper plate 1901 and lower plate 1903 can have segments (notshown) which extend backwards and into the deeper oropharynx withoutobstructing the center lumen.

For anti-device 1900, the bottom view (not shown) resembles the top view(FIG. 19A), except that instead of the upper plate 1901 and uppersegment 1911 of the top view, the lower plate 1903 and lower segment1913 would be seen.

Example 9B

In this example, an inventive anti-VAP mouthpiece device is madecompletely of a spongy and/or hydrogel absorptive material.

Example 9C

In this example, an inventive anti-VAP mouthpiece device is made of arelatively rigid material lined with a spongy and/or hydrogel absorptivematerial.

While the invention has been described in terms of its preferredembodiments, those skilled in the art will recognize that the inventioncan be practiced with modification within the spirit and scope of theappended claims.

What we claim as our invention is:
 1. An anti-ventilator associatedpneumonia (anti-VAP) mouthpiece device, comprising: an upper segment; alower segment, wherein said upper segment and said lower segment areconfigured for arrangement in an oral cavity of a patient and form abarrier that blocks passage of VAP-causing secretions into a lowerrespiratory tract of said patient; and an absorbent material forming atleast part of either or both said upper segment and said lower segment,said absorbent material being configured to absorb VAP-causingsecretions from at least said oral cavity of said patient, wherein saidupper segment and said lower segment define a center-hole configured topermit passage of an endotracheal tube (ETT) or a nasogastric tube andare configured so as not to obstruct a center pharyngeal lumen of saidpatient.
 2. The anti-VAP mouthpiece device of claim 1, wherein saidupper segment and said lower segment are configured to conform to dentaland proximal mucosal surfaces of said oral cavity of said patient. 3.The anti-VAP mouthpiece device of claim 1, wherein said lower segment isconfigured to cover at least part of lower dentition and gingival ofsaid patient.
 4. The anti-VAP mouthpiece device of claim 1, wherein saidlower segment includes a lower plate configured to cover a tongue ofsaid patient.
 5. The anti-VAP mouthpiece device of claim 1, wherein saidupper segment is configured to cover at least part of upper dentitionand gingival of said patient.
 6. The anti-VAP mouthpiece device of claim1, wherein said upper segment includes an upper plate configured tocover a hard/soft palate surface of said patient.
 7. The anti-VAPmouthpiece device of claim 1, further comprising side wings configuredto cover buccal mucosa of said patient.
 8. The anti-VAP mouthpiecedevice of claim 7, wherein said side wings are comprised at least partlyof absorbent material.
 9. The anti-VAP mouthpiece device of claim 7,wherein the side wings have a first segment extending upwardly to coveran upper dental and mucosal region and a second segment extenddownwardly to cover a lower dental and mucosal region.
 10. The methodanti-VAP mouthpiece device of claim 1, wherein said absorbent materialis saturated with antimicrobials or medicinals for sustained contact andreleaskey Currently amended e to at least one dentition or mucosalsurface of said patient.
 11. The anti-VAP mouthpiece device of claim 1,wherein said upper segment and said lower segment together form a solidmember which is a one-size-fits-all shape installable in adult patientsirrespective of tracheal diameter.
 12. The anti-VAP mouthpiece device ofclaim 1, wherein said upper segment and said lower segment together forma solid member which is a one-size-fits-all shape installable inpediatric patients irrespective of tracheal diameter.
 13. The anti-VAPmouthpiece device of claim 1, wherein the absorbent material comprisesmedicinals or antimicrobials.
 14. The anti-VAP mouthpiece device ofclaim 13, wherein said absorbent material is saturated withantimicrobials, and said antimicrobials are selected from the groupconsisting of chlorhexidine and hydrogen peroxide.
 15. The anti-VAPmouthpiece device of claim 1, wherein the absorbent material comprisesan anesthetic agent.
 16. The anti-VAP mouthpiece device of claim 1,wherein the absorbent material has capacity to absorb at least 0.1 ml or0.1 gm of secretions.
 17. The anti-VAP mouthpiece device of claim 1,wherein the absorbent material has capacity to absorb at least 1 ml or 1gm of secretions.